RISK FACTORS FOR YOUNG ADULT HODGKIN'S DISEASE IN TWINS

描述（由申请人提供）： 低出生顺序和低同胞的大小是年轻成人霍奇金病（YAHD）的强有力的危险因素。这些危险因素加上人口统计学模式（高社会阶层年轻白色成年人的危险性最高），使人联想到脊髓灰质炎的危险模式。病因机制可能涉及相对的社会隔离和保护，以避免暴露于常见的儿童感染，导致在青春期和青少年时期的易感性增加，后遗症更严重（HD可能是其中之一）。这种“卫生假说”被用来解释同胞人数与其他疾病（如哮喘）风险之间的关系。这可以解释观察到的与身高的相关性，因为儿童感染意味着更长的时间和更慢的生长。卫生假说很少被直接检验。我们建议通过使用YAHD不一致的双胞胎进行配对病例对照研究来做到这一点。受试者为210对双胞胎，其中一对双胞胎在11至50岁之间被诊断患有HD。我们将使用现有的问卷调查结果，比较双胞胎的感染情况和感染机会。比较将包括双胞胎之间在与其他儿童接触、特定儿童感染和潜在感染源方面的相对差异。我们预计感染/暴露较少的双胞胎是较高的双胞胎，双胞胎更有可能发展为YAHD。其他假设包括青春期提前、扁桃体切除术和传染性单核细胞增多症的影响。使用双胞胎病例和对照的优势包括减少基因组和早期环境的混淆，高依从性，对问题的共同理解，以及除了绝对响应之外提供直接病例对照比较的能力。我们有50-130个不一致对，每次暴露，并将能够检测比值比低至0.6和高达2.0，在80%的权力。将使用SAS中的多变量logistic回归进行匹配病例对照分析。

DESCRIPTION (provided by applicant): Low birth order and low sib-ship size are strong risk factors for young adult Hodgkin's disease (YAHD). These risk factors, combined with the demographic pattern (highest risk in young white adults of high social class), are reminiscent of the risk pattern for poliomyelitis. The etiologic mechanism may involve relative social isolation and protection from exposure to common childhood infections, leading to increased susceptibility later in the adolescence and teen years with more severe sequelae (of which HD may be one). This "hygiene hypothesis" has been used to explain the relationship between sib-ship size and risk of other diseases, such as asthma. It could explain observed associations with taller stature, since childhood infections mean longer periods of catabolism, and slower growth. The hygiene hypothesis has rarely been directly tested. We propose to do so by conducting a matched case-control study using twins discordant for YAHD. Subjects are 210 twin pairs in whom one twin was diagnosed with HD between the ages of 11 and 50. We will compare the twins' infections and opportunities for infection, using available questionnaire responses. Comparisons will include the relative difference between twins with respect to contact with other children, specific childhood infections, and potential sources of infection. We expect the twin with fewer infections/exposures to be the taller twin, and the twin more likely to develop YAHD. Additional hypotheses will include the effects of earlier puberty, tonsillectomy, and infectious mononucleosis. Advantages of using twin cases and controls include the reduction in confounding by the genome and early environment, high compliance, a common understanding of questions, and the ability to provide direct case-control comparisons in addition to absolute responses. We have between 50-130 discordant pairs for each exposure and will be able to detect odds ratios as low as 0.6 and as high as 2.0 at 80% power. A matched case-control analysis will be performed using multivariate logistic regression in SAS.